Ameliorative efficacy of Sepia officinalis ink extract on hepatorenal injury-induced following high-dose folic acid supplementation in rats

Sepia ink, a black suspension of melanin granules, is a multifunctional marine bioactive material. The present study aims to evaluate the ameliorative effect of the ink extract (IE) of the cuttlefish (Sepia officinalis) during high dosage administration of the FA in rats. Kidney injury induced by a single oral dose of FA (250 mg /kg). Eighteen male Wistar albino rats were the control, FA group, and FA+ IE group (250mg/kg). The IE showed a significant ameliorative effect against hepatorenal injury induced by high intake of FA as evident by decreasing the levels of serum aminotransferases (AST and ALT), urea, creatinine, uric acid, and significantly increased total serum albumin. Treatment with IE normalized the antioxidant status of the injured animals by reducing the MDA and the significant increase in the levels of GSH and CAT. The present study revealed that IE had an insightful effect against hepatorenal injury-induced following high intake of FA in rats, as it alleviates the alterations in the oxidative stress markers.

Effect of crude aqueous leaves extract of Bryophyllum Pinnatum on antioxidant status, blood glucose, lipid profile, liver and renal function indices in albino rats

Bryophyllum pinnatum is an important enthnomedicinal plant. The study assessed the effect of crude aqueous leaves extract of Bryophyllum pinnatum (CALEBP) on fasting plasma glucose (FPG), antioxidant status, lipid profile, liver and renal function indices in albino rats. The rats were housed under standard laboratory conditions (12h light: 12h dark photoperiod), 23± 2 ºC and were given rat pellets and tap water ad libitum. Twenty four rats weighing 190-232g were randomized into four groups (A-D) of six rats each. Group A (control) received normal feed and water only. Groups B, C and D received orally 180, 360 and 540 mg/kg body weight respectively of CALEBP for 28 days. Serum aminotransferases, alkaline phosphatase (ALP), superoxide dismutase, catalase, FPG, lipid profile, urea, creatinine, bilirubin, proteins, malondialdehyde, glutathione (GSH) and total antioxidant capacity (TAC) and electrolytes were assessed by standard methods. Data were analyzed using one-way analysis of variance and p<0.05 was considered statistically significant. Groups C and D had significantly lower FPG (p = 0.030; p = 0.01) and higher ALP (p = 0.01; p = 0.001) compared to the controls. Group D had significantly lower creatinine (p = 0.03) and K+ (p = 0.02) compared to control. Group B, C and D had significantly lower GSH (p = 0.020, p = 0.000 and p = 0.000) while group B had significantly higher TAC (p = 0.04) compared to the controls. Dosage of extracts correlated positively with ALP (r = 0.705, p = 0.000) and negatively with FPG (r = -0.603, p = 0.002), K+ (r = -0.563, p = 0.004), creatinine (r = -0.464, p = 0.022) and GSH (r = -0.786, p = 0.000). Bryophyllum pinnatum aqueous leaves extract could lower blood glucose, potassium and creatinine levels and may increase ALP activity and GSH depletion in high doses. Keywords: Bryophyllum pinnatum, aqueous leaf extract, dosage, effect assessment, Albino rats

PGC-1α Protects against Hepatic Ischemia Reperfusion Injury by Activating PPARα and PPARγ and Regulating ROS Production

Peroxisome proliferator-activated receptors (PPARs) α and γ have been shown to be protective in hepatic ischemia/reperfusion (I/R) injury. However, the precise role of PPARγ coactivator-1α (PGC-1α), which can coactivate both of these receptors, in hepatic I/R injury, remains largely unknown. This study was designed to test our hypothesis that PGC-1α is protective during hepatic I/R injury in vitro and in vivo. Our results show that endogenous PGC-1α is basally expressed in normal livers and is moderately increased by I/R. Ectopic PGC-1α protects against hepatic I/R and hepatocyte anoxia/reoxygenation (A/R) injuries, whereas knockdown of endogenous PGC-1α aggravates such injuries, as evidenced by assessment of the levels of serum aminotransferases and inflammatory cytokines, necrosis, apoptosis, cell viability, and histological examination. The EMSA assay shows that the activation of PPARα and PPARγ is increased or decreased by the overexpression or knockdown of PGC-1α, respectively, during hepatic I/R and hepatocyte A/R injuries. In addition, the administration of specific antagonists of either PPARα (MK886) or PPARγ (GW9662) can effectively decrease the protective effect of PGC-1α against hepatic I/R and hepatocyte A/R injuries. We also demonstrate an important regulatory role of PGC-1α in reactive oxygen species (ROS) metabolism during hepatic I/R, which is correlated with the induction of ROS-detoxifying enzymes and is also dependent on the activations of PPARα and PPARγ. These data demonstrate that PGC-1α protects against hepatic I/R injury, mainly by regulating the activation of PPARα and PPARγ. Thus, PGC-1α may be a promising therapeutic target for the protection of the liver against I/R injury.

Liver and COVID-19: possible mechanisms of damage

The global epidemic of a new coronavirus infection caused by SARS-CoV-2 is a major threat to human health. In the clinical picture, along with acute respiratory distress syndrome, liver lesions are also noted. The following mechanisms are currently being considered: direct damaging effects of SARS-CoV-2, immuno-mediated inflammation, hypoxia, drug exposure, and reactivation of pre-existing liver disease. We studied 150 patients with COVID-pneumonia who are under inpatient treatment at the University Clinical Hospital No. 1 of Sechenov First Moscow State Medical University. Of these, the presence of SARS-CoV-2 RNA was confirmed by polymerase chain reaction in 84 (56.0%) patients. In 55 (36.7%) patients, an increase in serum aminotransferases was registered, mainly alanine aminotransferase max. up to 572 U/L and aspartate aminotransferase up to a max. of 232 U/L. The long-term consequences are unknown and require monitoring of these patients.

Pregabalin, a GABA Analogue Protects against Carbon Tetrachloride-Induced Oxidative Stress and Liver Injury in Rats

Pregabalin is a synthetic analogue of the neurotransmitter g-aminobutyric acid (GABA) and is used in the treatment of epilepsy and neuropathic pain. The aim of this study was to investigate the effect of pregabalin on toxic liver injury caused by the acute administration of carbon tetrachloride (CCl4). Rats were orally treated with CCl4 for two successive days either alone or along with intraperitoneal pregabalin at doses of 7 and 14 mg/kg. The control group received the vehicle (olive oil). Liver oxidative stress and damage were assessed by determining serum and/or liver tissue levels of malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), DNA fragmentation, serum aminotransferases, paraoxonase-1 (PON-1), and hepatic histopathology. Results showed that CCl4 significantly (i) increased MDA and NO and decreased PON-1 in both serum and liver tissue, and (ii) decreased liver GSH content and induced marked hepatic DNA fragmentation. CCl4 treatment caused liver tissue injury as evidenced by significantly increased serum aminotransferases. In line with the above biochemical changes, the liver of CCl4-treated rats exhibited massive steatosis, vacuolar degeneration, cloudy swelling, and necrosis. In CCl4-treated rats, pregabalin given at the dose of 14 mg/kg significantly reduced the increments in MDA, NO, serum aminotransferases, and hepatic DNA fragmentation. Liver GSH was unaltered but hepatic and serum PON-1 activity increased after administering pregabalin which also improved, though not normalized, liver tissue histopathology. Collectively, these results suggest that the administration of pregabalin is associated with a reduction in experimental liver injury caused by CCl4. (First online: Apr 12, 2021)

Evaluation of the Impact of Ranolazine Treatment on Liver Function Tests in Patients With Coronary Heart Disease and Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is the most common liver pathology in the developed world. Nonalcoholic fatty liver disease is associated with a higher risk of cardiovascular disease. We investigated the impact of ranolazine on liver tests in patients with NAFLD and coronary artery disease (CAD). Patients who had established CAD and NAFLD (as assessed by raised serum transaminase activity, sonographic criteria, and the absence of any other obvious liver disease) were allocated to “on ranolazine” (n = 40) or “not on ranolazine” (n = 35) groups. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured in all patients at baseline and at the end of the study. After 6 months of ranolazine treatment, both ALT and AST activities were significantly lower in patients in the “on ranolazine” group compared with “not on ranolazine” patients (change from baseline: ALT, −11.0 ± 1.7 IU/L, P < .001; AST, −5.2 ± 1.9 IU/L, P =.009). In conclusion, the present study showed that treatment with ranolazine for 6 months led to a significant reduction in the activities of both serum aminotransferases in patients with stable CAD and NAFLD.

Outcomes of Early-onset Preeclampsia With Severe Features at the University Hospital in Southern Thailand: a 15-year Experience

Purpose: To evaluate outcomes and factors associated with adverse outcomes among patients with early-onset preeclampsia with severe features at Songklanagarind Hospital. Methods: A retrospective study of 326 singleton women with early-onset preeclampsia with severe features treated at Songklanagarind Hospital between 2004-2019 was conducted. Baseline characteristics, management and outcomes were reviewed. Multivariate logistic regression was used to evaluate predictors of adverse outcomes. Statistical significance was set at p < 0.05.Results: There were no maternal mortalities, with 3.1% stillbirths and 6.7% neonatal deaths. High maternal serum creatinine (OR 3.26, 95% CI 1.27-8.36, p = 0.01) was significantly associated with adverse maternal outcomes. Early gestational age at delivery [< 28 weeks (OR 16.63, 95% CI 6.95-39.80, p <0.01), 28-32 weeks (OR 3.24, 95% CI 1.54-6.85, p <0.01)], maternal diabetes mellitus (OR 5.62, 95% CI 1.43-22.06, p = 0.01), high maternal serum creatinine (OR 2.66, 95%CI 1.20-5.93, p = 0.02) and elevated serum aminotransferases (OR 2.26, 95% CI 1.19-4.29, p = 0.01) were associated with serious adverse perinatal outcomes.Conclusions: Early-onset preeclampsia with severe features had favorable outcomes. Maternal diabetes mellitus, high serum creatinine, elevated serum aminotransferases and early gestational age at delivery were factors associated with poor outcomes.

Gestation Food Restriction and Refeeding Compensate Maternal Energy Status and Alleviate Metabolic Consequences in Juvenile Offspring in a Rabbit Model

Nutritional status during gestation can influence mother and offspring metabolism. Undernutrition in pregnancy affects women in both western and developing countries, and it is associated with a high prevalence of chronic diseases in later life. The present work was conducted in the rabbit model, as a longitudinal study, to examine the effect of food restriction during early and mid-gestation, and re-feeding ad libitum until the end of pregnancy on metabolic status and body reserves of mother and, its association with development and metabolism of fetuses and female offspring to the juvenile stage. Little changes in live body weight (LBW), compensatory feed intake, similar body reserves, and metabolism were observed in dams. Placenta biometry and efficiency were slightly affected, but fetal BW and phenotype were not modified. However, hyperinsulinemia, insulin resistance, and hypertriglyceridemia were demonstrated in pre-term fetuses. In the juvenile period, these changes were not evidenced, and a similar pattern of growth and serum metabolic parameters in offspring of food-restricted mothers were found, except in serum aminotransferases levels, which increased. These were associated with higher liver fibrosis. Maternal food restriction in the early and mid-pregnancy followed by re-feeding in our rabbit model established a compensatory energy status in dams and alleviated potential long-term consequences in growth and metabolism in the offspring, even if fetal metabolism was altered.